Interleukin-4 is a prototypic type I cytokine that is a central regulator of immune/ inflammatory responses. It is particularly important in all aspects of allergic responses and allergic inflammation in its role as the switch factor controlling IgE production and as the major determinant of the differentiation of TH2 type CD4+ T cells. To understand how it mediates its functions and to develop strategies to control its actions, studies of the mechanisms through which interleukin-4 is induced, how its receptor is regulated, how its receptor transduces signals, and how it participates in the expression and maintenance of immunologic memory have been undertaken.The dynamics of IL-4 receptor signalling and the analysis of the functions of many of the signal transducing molecules activated by the receptor including Stat6, IRS-2, FRIP and dok are under active study with the goal of understanding in detail how the receptor orchestrates IL-4 functions. In parallel, an effort to gain structural information about the domains within the cytosolic region of the IL-4 receptor alpha chain has been initiated. In order, to understand how IL-4 producing cells are induced, systems for the purification of na?ve cells and the use of cells from mice defective in the IL-4 receptor have been undertaken. These studies indicate that endogenous production of IL-4 by na?ve cells can play a role in TH2 commitment, although they do so at a slow rate and probably are mainly important in circumstances in which TH2 induction is gradual rather than sudden. To analyze the expression of IL-4 at the molecular level, mice in which the gene for the green fluorescence protein (GFP) has replaced the first exon of the IL-4 gene have been prepared. Using techniques that allow the purification of cells producing IL-4 or expressing GFP, an analysis of the basis of commitment to cytokine-producing phenotype has been undertaken. These experiments suggest a system in which initial expression of IL-4 alleles is ?plastic? and stabilization of allele expression is a late, probably stochastic event. Studies of immunologic memory, including issues of compartment size, stability, and protection from activation induced cell death also are important aspects of this project. - Interleukin-4, Cytokines, Interferon gamma, Allergy, Autoimmune diseases, Stat6, TH2 Cells